Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain

  • Stevie C. Britch
    Address reprint requests to Stevie C. Britch, PhD, Center on Drug and Alcohol Research, University of Kentucky, Behavioral Science, 845 Angliana Avenue, Lexington, KY 40508.
    Center on Drug and Alcohol Research, University of Kentucky, Lexington, Kentucky

    Department of Behavioral Science, University of Kentucky, Lexington, Kentucky
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  • Rebecca M. Craft
    Department of Psychology, Washington State University, Pullman, Washington
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Published:September 15, 2022DOI:


      • Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) each reduced chronic inflammatory pain (allodynia and hyperalgesia) in rats.
      • CBD reduced some antinociceptive effects of THC, particularly in females.
      • CBD increased THC-induced sedation and anxiety-like effects in an open field test.


      Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), 2 of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the pain-relieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain. The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freund's adjuvant-induced inflammatory pain. After induction of hindpaw inflammation, vehicle, CBD (0.05–2.5 mg/kg), THC (0.05–2.0 mg/kg), or a CBD:THC combination (3:1, 1:1, or 1:3 dose ratio) was administered i.p. twice daily for 3 days. Then on day 4, mechanical allodynia, thermal hyperalgesia, weight-bearing, and locomotor activity were assessed 0.5 to 4 hours after administration of the same dose combination. Hindpaw edema and open field (anxiety-like) behaviors were measured thereafter. THC alone was anti-allodynic and anti-hyperalgesic, and decreased paw thickness, locomotion, and open field behaviors. CBD alone was anti-allodynic and anti-hyperalgesic. When combined with THC, CBD tended to decrease THC effects on pain-related behaviors and exacerbate THC-induced anxiety-like behaviors, particularly in females. These results suggest that at the doses tested, CBD-THC combinations may be less beneficial than THC alone for the treatment of chronic inflammatory pain.


      The present study compared CBD and THC effects alone and in combination in male and female rats with persistent inflammatory pain. This study could help clinicians who prescribe cannabis-based medicines for inflammatory pain conditions determine which cannabis constituents may be most beneficial.

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